- Chorea is a combination of fluid or jerky movement
affecting any part of the body; chorea can resemble a dance (from
Greek word), and movements are repetitive but not rhythmic or stereotyped.
Patients with chorea appear restless.
- Athetosis is a slow, writhing movement of the
limbs that may occur alone but is often associated with chorea (choreoathetosis).
- Ballismus is a high-amplitude, violent flinging
of a limb from the shoulder or pelvis and is considered to be an extreme
form of chorea.
Common causes of chorea are listed in Table
Table 566-1. Causes of Chorea ||Download (.pdf)
Table 566-1. Causes of Chorea
Benign familial chorea
Familial paroxysmal choreathetosis
Panthotenate-kinase deficiency (Hallervorden-Spatz disease)
Drug-induced movement disorders
Cardiopulmonary bypass surgery
Antiphospholipid antibody syndrome
Vitamin B12 deficiency
Tumors of cerebral hemispheres
Chorea is seen in 1% to 10% of children with congenital
heart disease following cardiopulmonary bypass surgery and profound hypothermia.1 The
mechanism of basal ganglia injury is unknown. Choreoathetosis begins
within 2 weeks postoperatively and may be associated with orofacial
dyskinesia, hypotonia, affective changes, and pseudobulbar signs.
Outcome varies; spontaneous resolution may occur, but significant
morbidity and even mortality may result. MRI of the brain is normal.
Treatment includes sedation in severe cases.
Drug-induced chorea is common after administration of dopamine
antagonists and is usually dose related. Chorea usually presents
in a form of tardive dyskinesia (TD). TD denotes
chorea that occurs late (tardive) in the course of the use of medication
or when medication is discontinued. This occurs commonly with chronic
use of neuroleptics. The incidence of TD in children taking neuroleptics
is estimated to be 1%.
TD often affects the region of the mouth and face and includes
chewing-like movements, tongue protrusion, and lip smacking. TD
can involve other parts of the body including the trunk and extremities.
Symptoms occur from months to years after starting therapy. The
condition should be suspected in any child who is chronically on
neuroleptics and should be distinguished from tics and Tourette
syndrome. TD should be treated by discontinuation of the offending
medication or by switching to an atypical neuroleptic. Addition
of benzodiazepines can be useful.
This is a rare disorder that presents with chorea in early childhood
and is inherited in an autosomal dominant pattern.2 Chorea
can be associated with delayed motor development, tremor, dysarthria,
and hypotonia. Children with this disorder have a positive family
history. The therapy recommended is low doses of neuroleptics.
Fahr disease is a combination of encephalopathy and progressive
calcification of basal ganglia. It may be familial or sporadic and
can be transmitted in an autosomal-dominant or autosomal-recessive
pattern. Patients present with chorea and mental deterioration.
Other clinical features can include ataxia, dysarhria, seizures, dwarfism,
senile appearance, and retinitis pigmentosa. Patient’s
symptoms progress into early disability and death. CT and MRI show
calcification in the basal ganglia. There is no specific therapy
for this disorder.
Disease (Panthotenate-Kinase Deficiency)
Panthotenase-kinase deficiency is a rare hereditary condition
of abnormal iron metabolism, transmitted in an autosomal-recessive
pattern. Patients are affected at 2 to 10 years of age, and clinical
manifestations include chorea, dystonia, rigidity, and dysarthria.
Other less common features include retinitis pigmentosa, seizures,
and mental retardation. Genetic testing is available to establish
the diagnosis and consists of a defect in the gene PANK2 on the
short arm of chromosome 20 encoding the enzyme Pantotenate Kinase
2.3 Neuroimaging studies often reveal a heterogeneous signal
intensity in the basal ganglia, which constitutes a feature highly
suggestive of this disorder (“eye-of-the-tiger”).4 Symptomatic
therapy with levodopa might improve symptoms of rigidity; anticholinergics can
improve dystonia. Symptoms usually progress, and death occurs in
the early 30s.
Chorea associated with SLE is an uncommon early presentation
of the disease. Clinical features are indistinguishable from Sydenham
chorea. Patients might have additional neurological symptoms such
as ataxia, psychosis, or seizures. The typical duration of the symptoms
is about 12 weeks, but one fourth of the patients have a recurrence.
The diagnosis is clear if the patient has history of LE; if chorea
is the initial presentation, it is important to differentiate it
from Sydenham chorea. Laboratory tests include elevation of sedimentation
rate and antinuclear antibodies. Therapy includes high doses of
SCH is the most common cause of acquired chorea in children and
occurs most commonly between ages 5 and 15 years. It is a cardinal
feature of rheumatic fever and is sufficient alone to make a diagnosis.
SCH usually occurs several weeks to months after untreated streptococcal
infection (beta hemolytic streptococcus). The disorder may result
from an abnormal immune reaction in which antibodies produced in
response to the invading bacterium act against basal ganglia.5
Patients may also present with hypotonia and behavioral changes.
The majority of patients will have gradual improvement of the symptoms
within weeks; recurrence of chorea is common, occurring in about
20% of patients. Rheumatic valvular disease develops in
about one third of untreated patients.
Diagnosis is made by the clinical presentation and cannot be
confirmed by laboratory tests. Because the onset of symptoms is
delayed for some time after infection, the antistreptolysin ASO
titer can be normal or only slightly elevated. Brain MRI may show
increased T2 signal in the putamen and globus pallidus, which resolves
when chorea resolves.6 All children with SCH must be treated
with penicillin in high doses for 10 days. Some experts suggest
that patients with acute rheumatic fever should be prophylactically
treated for 5 years up to age 18 (whichever comes first). A longer
period of prophylaxis is recommended only for those who have significant
rheumatic valvular heart disease (see Chapter 235).
Huntington disease (HD) is an autosomal dominant neurodegenerative
condition. The classic signs include chorea and dementia with personality
changes. Although symptoms typically become evident during the fourth
and fifth decades, the age of onset ranges from early childhood
to late adulthood.
HD is transmitted as an autosomal dominant trait. The disorder
occurs as the result of abnormally long CAG repeats of coded instructions within
a gene on chromosome 4 (4p16.3).7The progressive loss
of nervous system function associated with HD results from loss
of neurons in the basal ganglia and cerebral cortex. Juvenile HD
is called Westphal variant and presents with rigidity, bradykinesia,
dystonia, myoclonus, tremor, behavioral problems, and seizures.
Dystonia is an involuntary muscle contracture
caused by simultaneous contracture of agonist and antagonist muscle
which causes twisting of various body parts (face, neck, limb, and
trunk). Dystonia can produce writhing involuntary movements or can
cause fixed abnormal posture. Dystonia can affect a single body
part (focal dystonia), 2 or more contiguous body parts (segmental
dystonia), the arm and leg on one side of the body (hemidystonia),
or multiple body parts (generalized dystonia). Most dystonia in
children begins focally and spreads over time to the rest of the
body. A characteristic feature of dystonia is a presence of “sensory
tricks” (gestes antagonists). Patients can temporarily suppress
dystonic movements by those tricks. These tricks usually consist
of touching the affected or adjacent body parts.
Classification of dystonia has been based upon etiology, age
of onset, or body part affected. Historically, dystonia has been
divided into primary (idiopathic) and secondary. In the future,
classification may rely entirely on identification of genetic defects
that either cause the disease or provide predisposition to the development
of dystonia (eTables 566.1, 566.2, and 566.3).
eTable 566.1. Classification
of Dystonia ||Download (.pdf)
eTable 566.1. Classification
|Age of Onset||Body Part Affected|
566.2. Genetic Causes of Dystonia (DYT Scheme) ||Download (.pdf)
566.2. Genetic Causes of Dystonia (DYT Scheme)
|DYT1||Oppenheim dystonia (dystonia musculorum deformans)||Torsin A|
|DYT2||Autosomal recessive PTD||Unknown|
|DYT3||X-linked dystonia/parkinsonism (Lubag)||TATA box BPAF1|
|DYT4||Australian whispering dysphonia||Unknown|
|DYT6||Adolescent onset, mixed/segmental||Unknown|
|DYT7||Adult onset, focal||Unknown|
|DYT8||Paroxysmal dystonic choreoathetosis||Myofibrillogenesis RP|
|DYT10||Paroxysmal kinesigenic choreoathetosis||Unknown|
|DYT12||Rapid-onset dystonia Parkinsonism||Na+/K+ ATPase|
|DYT13||Italian focal/segmental dystonia||Unknown|
|DYT14||Dopa-responsive dystonia type 2||Unknown|
|DYT15||Canadian myoclonus dystonia||Unknown|
566.3. Other Genetic and Nongenetic Causes of Dystonia ||Download (.pdf)
566.3. Other Genetic and Nongenetic Causes of Dystonia
|Autosomal Recessive||Autosomal Dominant||Mitochondrial|
|AADC deficiency||DRPLA||Leber disease|
|Ataxia teleangiectasia||Familial parkinsonism||Leigh syndrome|
|Ceroid lipofuscinosis||Frontotemporal dementia||MERRF|
|Gangliosidoses||Hereditary spastic paraplegia with dystonia||MELAS|
|Glutaric aciduria||Huntington disease|
|Hartnup disease||Spinocerebellar ataxias|
|Methylmalonic aciduria||Dystonia-deafness||Autoimmune (ADEM)|
|Nieman-Pick type C||Lesh-Nyhan||Cerebral palsy|
|PKAN (Hallervorden-Spatz)||Pelizaeus Merzbacher||Drugs|
|TH deficiency||Rett syndrome||Infection|
|Vitamine E deficiency||Stroke|
Dystonia has been associated with a number of diseases, but there
is often no discrete, identifiable pathological abnormality in the brain.
There is, however, evidence indicating that it is caused by dysfunction
of the nigrostriatal dopamine system in the basal ganglia.
The most common dystonias encountered in children are dopa-reponsive
dystonia and idiopathic generalized torsion dystonia.
Dystonia (Segawa Disease, DRD)
DRD is the most common cause of primary dystonia with onset in childhood.
DRD presents with gait disturbance as a result of foot dystonia.
The symptoms show diurnal variation with worsening later in the
day and marked improvement in the morning. If dystonia remains untreated,
parkinsonian symptoms may also develop later in the course of the
illness. The age group most commonly affected is 1 to 12 years.
Characteristically, DRD shows a dramatic response to low doses of
L-dopa, without development of long-term treatment complications.
DRD is caused either by GTP cyclohydrolase deficiency (more common)
or by tyrosine hydroxylase (TH) deficiency.8,9 GTP cyclohydrolase
is the initial and rate-limiting enzyme involved in the biosynthesis
of tetrahydrobiopterin (BH4), which is a cofactor for tyrosine hydroxylase,
the rate-limiting enzyme in dopamine synthesis. The most common
type of inheritance is autosomal dominant. Diagnosis is made by
Dystonia (ITD, Dystonia Musculorum Deformans)
ITD is an autosomal dominant condition with incomplete penetrance.
The cause of ITD is GAC deletion in the DYT-1 gene at 9q34.10 The
product of the DYT-1 gene is called torsin A.11
Symptoms of ITD may appear early in life at about 9 years of
age but may be delayed until about 45 years or later. Dystonia usually first
occurs in the limbs as a focal dystonia, but over time spreads to become
generalized. Trunk dystonia is a characteristic feature in younger
patients. Patients do not have other neurological symptoms, and
they do not develop mental deterioration.
Therapy usually considered is a trial of levodopa, but this medication
is not effective in ITD. Trihexyphenidyl can be beneficial, as well
as baclofen and diazepam. Deep brain stimulation surgery in the
globus pallidus pars interna brought promising results in therapy
of this debilitating disorder.
Glutaric acidemia type I presents with an acute encephalitis-like
illness with somnolence, irritability, subsequent development of
chorea and dystonia. Diagnosis and treatment are discussed in Chapter 140.
Glutaric academia type I is a rare inborn error in the catabolism
of lysine, hydroxylisine, and tryptophan. It is transmitted by autosomal
recessive inheritance and is caused by deficiency of glutaryl-coenzyme
A dehydrogenase. Clinically, patients present with an acute encephalitis-like illness
with somnolence, irritability, and afterwards they develop chorea
and dystonia. Diagnosis is made by the presence of abnormal amounts
of glutaric acids in the urine. Therapy might include protein restriction
and riboflavin supplementation.
Tremor is an involuntary oscillating movement
with a fixed frequency. The most common cause of tremor in children
is essential (familial) tremor. Essential tremor
(ET) is transmitted in autosomal dominant trait.12 Patients
with ET at young onset do not develop other neurological symptoms. Shuddering
attacks may occur in young children and are considered to be forms
of ET.13 ET can occur as early as 2 years of age. The most
commonly involved areas of the body are the hands and the head;
voice is also commonly affected. Tremor occurs mainly in association
with action and is worse with anxiety. Therapy is recommended only
in significantly affected individuals; it includes use of propranolol
and primidone. Wilson disease is a rare cause of tremor in children.
Diagnosis and management are discussed in Chapter 573.
Wilson disease (hepatolenticular degeneration)
is a rare cause of tremor in children. It is an autosomal recessive
disorder due to mutation of ATP7B gene on chromosome 13 (13q14.3) producing
abnormal copper accumulation in the body.14 Copper initially
accumulates in the liver and later in other organs, particularly
the brain, eyes, and kidneys.
Neurological symptoms of Wilson disease usually do not occur
before the age of 10 years. Patients present with flapping hand
tremor, tremor of the head, voice, dystonia, bradykinesia, ataxia,
gait imbalance, and psychiatric problems. Diagnosis is made by measuring low
ceruloplasmin level and high serum and urine copper levels, also
by presence of Kayser-Fleischer ring (goldish ring around the cornea
of the eye). Therapy consists of administration of chelating agents
(D-penicillamine, trientene) and zinc acetate, which blocks the
absorption of copper in the intestines and promotes the elimination
of copper in the stool (see Chapter 421).
Myoclonus consists of sudden, brief, shock-like movements. These
movements may be “positive” or “negative” (asterexis). Positive
myoclonus results in contracture of a muscle or multiple muscles.
In asterexis, there is a brief loss of muscle tone and then contraction
of the muscles resulting in a flapping-type motion. Myoclonus can
be rhythmic or nonrhythmic, focal, multifocal, or generalized, and
can be activated by movement or sensory stimulation. Myoclonus is
classified as physiologic, essential, epileptic, and symptomatic
myoclonus (eTable 566.4).15
eTable 566.4. Etiologic
Classification of Myoclonus ||Download (.pdf)
eTable 566.4. Etiologic
Classification of Myoclonus
|Physiologic myoclonus||Sleep jerks and nocturnal myoclonus|
|Symptomatic myoclonus||Postcentral nervous system injury|
|Basal ganglia degenerations|
|Idiopathic torsion dystonia|
|Lysosomal storage disease|
Physiologic myoclonus occurs in normal people when falling asleep,
during sleep and during waking. Epileptic myoclonus is associated
with epileptiform activity on EEG. Essential myoclonus is a chronic
condition of focal, segmental, or generalized jerking that is aggravated
by action. Onset is between the first and second decade. A family history
of myoclonus may be obtained, but sporadic cases occur. Treatment
recommended is clonazepam, or several antiepileptic medications
such as levetiracetam, clonazepam, valproic acid, primidone, piracetam,
Symptomatic myoclonus has various causes (eTable
566.4). Posthypoxic myoclonus (Lance-Adams syndrome) is a form
of action myoclonus found in patients after an episode of hypoxia
and is lifelong. Medications such as valproate, 5-hydroxytryptopha,
or clonazepam may be helpful in symptomatic treatment of this type of
Tics and Tourette
Tics are involuntary, sudden, rapid, repetitive,
nonrhythmic, stereotyped movements (motor tics) or
sounds (vocal tics). Tics can present in a variety
of forms and have different degrees of severity and duration. Tics can present as simple tics
such as eye blinking or shoulder shrug, or complex such
as a stereotyped sequence of movements (touching, hitting, and smelling).
Complex vocalization includes syllables, phrases, echolalia (repeating
other people’s words), palilalia (repeating one’s own
words), or coprolalia (obscene words).16 Tics have certain
characteristic features such as a fluctuating course, suggestible
nature, exacerbation during periods of anticipation and emotional
upset, reduction when absorbed in activities, premonitory sensation
(in a form of an urge, impulse, tension), and voluntary suppressibility.
Tics can be divided into 2 major categories based on their duration: transient (present
less than 12 months) and chronic (present for more
than 12 months).17 Based on etiology, tics can also be divided
into primary (idiopathic), such as Tourette syndrome, chronic
motor tic disorder, chronic vocal tic disorder, and transient tic disorder,
and secondary, such as related to infection, drugs,
toxins, and developmental and chromosomal disorders18 (eTable 566.5). Drug- or toxin-induced
tics can be caused by stimulants, carbamazepine, steroids, neuroleptics,
and carbon monoxide. Parainfectious tics can occur
after streptococcus infection (PANDAS: postinfectious autoimmune
neuropsychiatric disorder associated with streptococcus infection).
Tics can also be seen with certain genetic and neurodegenerativedisorders.
eTable 566.5. Causes
of Tics ||Download (.pdf)
eTable 566.5. Causes
|Transient motor and phonic tics (< 1 year)|
|Chronic motor or phonic tics (> 1 year)|
|Adult-onset (recurrent) tics|
|Neurodegeneration with brain iron accumulation
|Duchenne muscular dystrophy|
|Infectious: encephalitis, Creutzfeldt-Jacob
disease, neurosyphilis, Sydenham disease|
|Drugs: amphetamines, methylphenidate, pemoline,
levodopa, cocaine, carbamazepine, phenytoin, phenobarbital, lamotrigine,
antipsychotics, and other dopamine receptor–blocking drugs
(tardive tics, tardive tourettism)|
|Toxins: carbon monoxide|
|Developmental: static encephalopathy, mental
retardation syndromes, chromosomal abnormalities, autistic spectrum disorders
|Chromosomal disorders: Down syndrome, Kleinfelter
syndrome, XYY karyotype, fragile-X, triple-X and 9p mosaicism, partial
trisomy 16, 9p monosomy, citrullinemia, Beckwith- Wiedemann syndrome|
|Other: Head trauma, stroke, neurocutaneous syndromes,
schizophrenia, neurodegenerative diseases|
Tourette syndrome (TS) represents only 1 entity
in a spectrum of tic disorder. TS presents with multiple motor and
at least 1 vocal tic, a waxing and waning course, with tics evolving
in a progressive manner; the presence of tic symptoms for at least
1 year, the onset of symptoms before age 21, the absence of precipitating
illnesses or medication, and the observation of tics by a medical professional.19
Tics are very common in children, more often seen in boys, and
most of them resolve spontaneously and do not require treatment unless
they interfere with school and social interactions. The prevalence
of moderately severe cases is estimated as 1 to 10/1000
children and adolescents.20,21 Onset of tics occurs any
time from 2 to 15 years of age. Neck muscles are often affected
first. New tics can occur in addition to or in place of an existing
tic and can affect the head, eyes, and face. Common tics include
eye blinking, grimacing, lip smacking, and shrugging of 1 or both
shoulders. Verbal tics include a clearing of the throat, snorting
or sniffing noise, and cough-like noise.
Many patients with tics have associated psychopathology that
includes attention deficit disorder (ADD) and obsessive-compulsive
disorder (OCD).22 ADD is characterized by hyperactivity,
short attention span, restlessness, poor concentration, and impaired
impulse control. OCD is characterized by ritualistic behavior and
thoughts. Typical OCD behavior includes placing objects repetitively
in a certain place, washing hands, obsessive thoughts of violence,
and counting objects.
The cause of tics is unknown; however, several family members
may be affected, suggesting a genetic component.23 Convincing
evidence exists that cortico-striatal-thalamo-cortical pathways
are involved in the expression of TS and tics and accompanying neuropsychiatric problems.24,25 The
precise pathophysiologic location of tics remains unknown.
Diagnosis of tics and TS is based on the history and clinical
examination. It is important for the examiner to observe the patient
or a videotape of the tics. A complete neurological examination
is essential to exclude other organic etiologies of abnormal movement. Brain
MRI and EEG are normal.
Many tics do not require therapy. The approach to treatment should be
directed to improving quality of life. If tics are severe, the treatment
should try to eliminate them during school hours; the dose of medication
can be decreased or discontinued during summer months or when the
child is not under stress. If pharmacological therapy is indicated,
2 categories of medications are available: nonneuroleptic drugs
for milder tics and typical/atypical neuroleptics for more
severe tics26 (Table 566-2). Botulinum
toxin27,28 has been used in treating motor and vocal tics,
and deep brain stimulation surgery (DBS) was also recently proposed
for use in severe disabling cases of TS.29,30
Table 566-2. Medication
for Tics ||Download (.pdf)
Table 566-2. Medication
|Neuroleptic medications||Typical neuroleptics:|
Symptoms of OCD are treated with selective serotonin reuptake
inhibitors (SSRIs) such as fluoxetine, sertraline, citalopram, or
tricyclic antidepressants. Behavioral therapy can be used to reduce
the frequency of compulsions.31 ADD is treated with CNS
stimulants such as methylphenidate or dextroamphetamine,32 α2-adrenergic
agonists (clonidine, quanfacine), and tricyclic antidepressants.33
Stereotypies are broadly defined as involuntary, patterned, coordinated,
repetitive, nonreflexive movements that are purposeless and occur
in exactly the same manner with each repetition (eg, recurrent arm
flapping, hand waving, finger wiggling, body rocking, leg shaking).34 Stereotypies
can be classified as physiologic or pathologic. Physiologic
stereotypies (rocking, thumb sucking, lip or cheek biting)
imply that the individual is otherwise normal and suggest a developmental
problem that may improve with maturation of the nervous system.
Stereotypies begin in infancy or early childhood; movements last seconds to minutes, tend to occur
in clusters, appear many times per day, have a fixed pattern, and
are associated with periods of excitement, stress, fatigue, or boredom.
Movements can be simple or complex and can be suppressed by a sensory
stimulus or distraction. The underlying pathophysiologic mechanism
is unknown. Therapy is usually not indicated.
Pathologic stereotypies occur in patients with
mental retardation, autism, Rett syndrome, neuroacanthocytosis,
schizophrenia, obsessive-compulsive disorder, Tourette syndrome,
and tardive dyskinesia.35